This subproject will investigate the development of T cell MHC restriction in the human allogeneic bone marrow transplant chimera, as it relates to dendritic cell engraftment and function. Allogeneic bone marrow transplantation is the only curative treatment available to patients with chronic myelogenous leukemia, as well as selected disorders of hematopoiesis or immunologic function; and it is an effective form of post-remission therapy for many patients with acute leukemia and certain lymphomas. Unfortunately, allogeneic bone marrow transplantation is largely restricted to those patients with genotypically HLA identical sibling donors. The use of alternative donors, i.e., partially mismatched related or matched and mismatched unrelated, places patients as significantly increased risks of graft rejection or graft-vs-host disease, as well as prolonged post-transplant immune suppression and its untoward sequelae. A major concern is that donor T cell progeny may acquire MHC restrictions unique to host, yet later be presented antigen only in the context of donor MHC on donor-derived antigen-presenting cells. Dendritic cells constitute a trace population of marrow derived leukocytes, uniquely specialized for efficient and potent antigen presentation. Despite extensive data substantiating the essential role of these cells in the primary sensitization and activation of T lymphocytes, as well as the central involvement of T cell immune responses in transplantation, there is a paucity of information relating the two in human transplantation biology. It is entirely unknown how dendritic cell chimerism may influence the development of T cell MHC restriction in this setting. The human bone marrow chimera presents a unique opportunity to evaluate the biology of dendritic cell-T lymphocyte interactions, despite the limitations imposed by using an outbred human population. The ontogeny and kinetics of dendritic cell engraftment, the development of MHC restriction among donor T cell progeny correlated with clinical immune function, and the identification of dendritic cell marrow progenitors and the conditions supporting their growth, are all important unknowns. An improved understanding of the biologic mechanisms involved is clearly needed if bone marrow transplantation is ever to achieve wider applicability beyond genotypically MHC-identical siblings.